Diacerein, [4,5-bis(acetyloxy)-9,10-dioxo-2-anthracene carboxylic acid]) is a highly purified anthraquinone derivative. It has been approved as a SYmptomatic Slow-Acting Drug in Osteoarthritis (SYSADOA) in several countries. Rhein is the major active metabolite of diacerein. Rhein has been shown to control the blood glucose concentration in type 2 (or type II) diabetes rodent models. However, no studies indicated that diacerein can control blood glucose in humans with type 2 diabetes. No literature has reported that diacerein can be used as adjunctive therapy for treating type II diabetes patients with inadequate drug response to current antidiabetic therapies.
The prevalence of diabetes has increased throughout the world. About seven percent of the population between 45-64 years old has diabetes and the number significantly increases in the population over 65 years old. There are two forms of diabetes. In the form of the disease known as type II, non-insulin dependent diabetes (NIDDM) or adult-onset (as opposed to juvenile diabetes or type I), it is a disorder which is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. The pancreas in type II diabetic patients often continues to secrete insulin. However, this insulin is ineffective in preventing the symptoms of diabetes which include the rise of cardiovascular risk factors such as hyperglycemia, hypertension, hypertriglycemia, high serum low-density-lipoprotein (LDL) cholesterol concentrations, low serum high-density-lipoprotein (HDL) cholesterol concentrations, impaired carbohydrate metabolism, glycosuria, decreased insulin sensitivity, and centralized obesity. Many of these cardiovascular risk factors are known to precede the onset of diabetes by as much as a decade. The symptoms of type II diabetes have led to severe complications, including macrovascular complications (coronary artery disease, peripheral arterial disease, and stroke) and microvascular complications (retinopathy, nephropathy, and neuropathy). The importance of blood glucose control and maintenance of glycated hemoglobin A1C (HbA1c) below 7.0% in preventing diabetic complications is now recognized.
A number of antihyperglycemic agent classes, each with its unique mechanism of action, have been introduced during the past several years: sulfonylureas, bisguanides, alpha-glucosidase inhibitors, thiazolidinediones (TZDs), Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), nonsulfonylurea insulin secretagogues, glucagon-like peptide-1 analog and insulin. According to clinical guidelines, first line blood glucose lowering therapy of type II diabetes is metformin or sulfonylurea monotherapy. However, monotherapy with metformin or sulfonylurea is of limited benefit. Only about 44% of patients maintain HbA1c below 7% after receiving the treatment for three years, and only 13% of patients maintain the level after nine years. If first line treatment is unsatisfactory, patients are moved to second line combination therapies such as metformin with sulfonylurea. In patients failing monotherapy with either agent alone, only about 30% of the patients treated with the combination or second line therapy of metformin with sulfonylurea, achieve HbA1c below 7% after two years of treatment. If this kind of therapy is still insufficient for patients to control blood glucose, then DPP-4 inhibitors, thiazolidinedione, glucagon-like peptide-1 analogs, meglitinides, alpha-glucosidase inhibitors, and/or insulin can be added to the second line treatment.
Despite the existence of anti-diabetic drugs, some patients cannot achieve the treatment goals. Accordingly, there is still a need for a new agent which effectively improves glycemic control of type II diabetes.